RESUMO
Pure partial duplications of the long arm of chromosome 16 are rare and few cases are described with delineation by chromosomal microarray. Data about clinical abnormalities of pure partial 16q duplications are incomplete because many individuals die during the perinatal period. We describe the clinical features of a 47-month-old Brazilian girl with 16q21q24.1 duplication. To the best of our knowledge, she is the first person with this specific chromosome segment duplication, and we compare her phenotype with the only reported individual alive with intermediate-distal pure 16q duplication.
Assuntos
Anormalidades Múltiplas/genética , Transtornos Cromossômicos/genética , Duplicação Cromossômica , Cromossomos Humanos Par 16/genética , Brasil , Pré-Escolar , Bandeamento Cromossômico , Feminino , Humanos , FenótipoRESUMO
Variants in MBTPS1 (membrane-bound transcription factor peptidase, site 1) encoding the protein convertase site-1 protease (S1P) were recently reported in a single individual with skeletal dysplasia and elevated plasma lysosomal enzymes. Here, we report the second individual with this newly described autosomal recessive spondyloepiphyseal dysplasia (OMIM #618392), presenting severe growth retardation, cataract and dysmorphic features, mainly retromicrognathia. Epilepsy and craniosynostosis were novel findings in our proband. She was found to be homozygous for a novel nonsense variant p.Trp983Ter in MBTPS1. In addition, she had normal levels of lysosomal enzyme activity in leukocytes but elevated levels in plasma. Our description confirms the existence of this new skeletal dysplasia and expands the phenotype and genotype of the disease.
Assuntos
Catarata/genética , Doenças por Armazenamento dos Lisossomos/genética , Lisossomos/genética , Pró-Proteína Convertases/genética , Serina Endopeptidases/genética , Catarata/diagnóstico por imagem , Catarata/patologia , Pré-Escolar , Feminino , Humanos , Doenças por Armazenamento dos Lisossomos/sangue , Doenças por Armazenamento dos Lisossomos/diagnóstico por imagem , Doenças por Armazenamento dos Lisossomos/patologia , Lisossomos/enzimologia , Linhagem , FenótipoRESUMO
Gillespie syndrome (GS) [MIM: 206700] is a very rare condition characterized by bilateral iris defect, congenital hypotonia, cerebellar ataxia and intellectual disability. The typical iris anomaly is considered necessary to the diagnosis of GS. Recently, variants in ITPR1 were described causing GS. Non-neurological features were reported in few patients. Here we describe two consanguineous siblings with GS and a novel homozygous ITPR1 pathogenic variant (p.N984fs). They also present a cardiac defect (pulmonary valve stenosis) and one sib had a genitourinary malformation (ureteropelvic junction obstruction). Our report reinforces ITPR1 as the cause of GS and suggests a possible role of ITPR1 in the development of other organs.
Assuntos
Aniridia/genética , Aniridia/patologia , Ataxia Cerebelar/genética , Ataxia Cerebelar/patologia , Homozigoto , Receptores de Inositol 1,4,5-Trifosfato/genética , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Mutação , Brasil , Pré-Escolar , Consanguinidade , Feminino , Humanos , Lactente , Masculino , Linhagem , IrmãosRESUMO
Sotos syndrome (SoS) is a multiple anomaly, congenital disorder characterized by overgrowth, macrocephaly, distinctive facial features and variable degree of intellectual disability. Haploinsufficiency of the NSD1 gene at 5q35.3, arising from 5q35 microdeletions, point mutations, and partial gene deletions, accounts for a majority of patients with SoS. Recently, mutations and possible pathogenetic rare CNVs, both affecting a few candidate genes for overgrowth, have been reported in patients with Sotos-like overgrowth features. To estimate the frequency of NSD1 defects in the Brazilian SoS population and possibly reveal other genes implicated in the etiopathogenesis of this syndrome, we collected a cohort of 21 Brazilian patients, who fulfilled the diagnostic criteria for SoS, and analyzed the NSD1 and PTEN genes by means of multiplex ligation-dependent probe amplification and mutational screening analyses. We identified a classical NSD1 microdeletion, a novel missense mutation (p.C1593W), and 2 previously reported truncating mutations: p.R1984X and p.V1760Gfs*2. In addition, we identified a novel de novo PTEN gene mutation (p.D312Rfs*2) in a patient with a less severe presentation of SoS phenotype, which did not include pre- and postnatal overgrowth. For the first time, our study implies PTEN in the pathogenesis of SoS and further emphasizes the existence of ethno-geographical differences in NSD1 molecular alterations between patients with SoS from Europe/North America (70-93%) and those from South America (10-19%).
RESUMO
BACKGROUND AND PURPOSE: Hyperargininemia (HA) is a rare autosomal recessive metabolic disorder and the neuroimaging features of this disease have seldom been reported. Hyperammonemic encephalopathy is uncommon in HA, and the clinical presentation of HA is distinct from other urea cycle disorders. This paper describes the brain MRI findings and a magnetic resonance spectroscopy (MRS) study of a series of Brazilian HA patients. METHODS: Brain MR images were obtained in eight male and two female patients with the classic HA phenotype. Six patients were evaluated twice. Single-voxel (1)H-MRS was also performed in six of the patients. RESULTS: Only 1 patient, with less severe neurological symptoms, had normal MRI images. A variable degree of cerebral atrophy was noted in the other patients, and 3 patients also presented mild symptoms of cerebellar atrophy. MRS indicated no metabolic abnormalities in any patient. CONCLUSIONS: We present the MRI and MRS findings of a large series of HA patients. Variable degrees of brain atrophy and mild cerebellar atrophy were observed, and these findings were not specific. No metabolic abnormality was observed using MRS in this series of patients.
Assuntos
Arginina/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Hiperargininemia/diagnóstico , Hiperargininemia/metabolismo , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Prótons por Ressonância Magnética/métodos , Adolescente , Adulto , Atrofia , Biomarcadores/metabolismo , Criança , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
Hyperargininemia is an autosomal recessive metabolic disorder caused by a deficiency of enzyme arginase I. It is a rare pan-ethnic disease with a clinical presentation distinct from that of other urea cycle disorders, and hyperammonemic encephalopathy is not usually observed. Hyperargininemia is one of the few treatable causes of pediatric spastic paraparesis, and can be confused with cerebral palsy. We retrospectively evaluated the clinical onset, neurologic manifestations, progression of abnormalities, electroencephalographic abnormalities, and laboratory findings of 16 Brazilian patients with hyperargininemia. Relevant data about the clinical spectrum and natural history of hyperargininemia are detailed. Progressive spastic diplegia constituted the key clinical abnormality in this group, but variability in clinical presentation and progression were evident in our series. Seizures in hyperargininemia may be more common than reported in previous studies. Features distinguishing hyperargininemia from cerebral palsy and hereditary spastic paraplegia are emphasized in this large series of patients.
Assuntos
Progressão da Doença , Hiperargininemia/diagnóstico , Hiperargininemia/fisiopatologia , Adulto , Paralisia Cerebral/diagnóstico , Paralisia Cerebral/fisiopatologia , Criança , Eletroencefalografia/métodos , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Convulsões/diagnóstico , Convulsões/fisiopatologia , Paraplegia Espástica Hereditária/diagnóstico , Paraplegia Espástica Hereditária/fisiopatologia , Adulto JovemAssuntos
Hipertensão Pulmonar/etiologia , Mandíbula/anormalidades , Miosite Ossificante/complicações , Apneia Obstrutiva do Sono/etiologia , Adolescente , Criança , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Mandíbula/diagnóstico por imagem , Miosite Ossificante/fisiopatologia , Polissonografia , Apneia Obstrutiva do Sono/fisiopatologia , Tomografia Computadorizada por Raios XRESUMO
Spinocerebellar ataxia type 3, or Machado-Joseph disease, is an autosomal dominant neurodegenerative disease characterized by a wide spectrum of clinical findings that include progressive cerebellar ataxia. All affected individuals have an expanded CAG repeat mutation in one allele of the ATXN3 gene. An inverse relationship exists between the age of onset and the number of repeats in the abnormal expanded allele. The case described is that of a child with Machado-Joseph disease, daughter of a consanguineous affected couple. She inherited the expanded allele in homozygosity with CAG repeat size similar to that of her parents, and had a distinct early onset (4 years of age) and severe clinical phenotype. This case supports the conclusion that homozygosity aggravates the clinical phenotype. Loss of function of the normal expressed ataxin-3, or possibly aggregation of ataxin-3, may be implicated in disease mechanism.
Assuntos
Homozigoto , Doença de Machado-Joseph/genética , Doença de Machado-Joseph/patologia , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Ataxina-3 , Pré-Escolar , Feminino , Humanos , Linhagem , Fenótipo , Índice de Gravidade de DoençaRESUMO
Prader-Willi syndrome is a mental retardation genetic disorder also characterized by hypogonadism, hyperphagia and obesity. We report on a four-years-old boy, born to consanguineous parents, with uncommon co-occurrence of Prader-Willi syndrome, 47,XXY karyotype (Klinefelter syndrome) and coronal craniosynostosis. These are different unrelated conditions and it was not described before in the same patient to the best of our knowledge.
Assuntos
Craniossinostoses/genética , Síndrome de Klinefelter/genética , Síndrome de Prader-Willi/genética , Pré-Escolar , Craniossinostoses/complicações , Humanos , Síndrome de Klinefelter/complicações , Masculino , Síndrome de Prader-Willi/complicaçõesRESUMO
A síndrome de Prader-Willi é afecção genética de deficiência mental associada a hipogonadismo hipogonadotrófico, hiperfagia e obesidade. Descrevemos o caso de menino de 4 anos de idade, filho de casal consangüíneo, apresentando três condições clínicas não relacionadas: síndrome de Prader-Willi, cariótipo 47,XXY (compatível com síndrome de Klinefelter) e craniossinostose coronal. Ao nosso conhecimento, não foi relatado caso semelhante previamente na literatura.
Assuntos
Pré-Escolar , Humanos , Masculino , Craniossinostoses/genética , Síndrome de Klinefelter/genética , Síndrome de Prader-Willi/genética , Craniossinostoses/complicações , Síndrome de Klinefelter/complicações , Síndrome de Prader-Willi/complicaçõesRESUMO
Investigators of independent studies reported alterations in cytokine serum levels in patients with different mood disorders. Several polymorphisms associated with neuropsychiatric disorders such as schizophrenia and Alzheimer's disease have been reported at the interleukin-1 (IL-1) panel. Here we report the results of three specific polymorphisms at the IL-1alpha, IL-1beta, and IL-1RA genes, which were analyzed in 128 Brazilian subjects: 59 dysthymic patients and 69 normal controls. We found a statistically significant difference (p = 0.002) in the frequency of haplotypes with alleles 2+ (IL-1RA), T+ (IL-1alpha), and C+ (IL-1beta) in patients as compared to controls. We also observed that haplotype IL-1RA1.2/IL-1alpha CT/IL-1beta CC, present in 6 dysthymic patients (10%) was absent in the normal control group (p = 0.012). These results suggest that these polymorphisms might confer a greater susceptibility to develop dysthymia in Brazilian patients. However, to validate these data it will be of great interest to repeat this study in larger samples and other ethnic groups.